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Maintaining Bone Health
in Patients With Multiple Myeloma:
Survivorship Care Plan of the International Myeloma
Foundation Nurse Leadership Board
Teresa S. Miceli, RN, BSN, OCN®, Kathleen Colson, RN, BSN, BS, Beth M. Faiman, MSN, APRN-BC, AOCN®,
Kena Miller, RN, MSN, FNP, Joseph D. Tariman, PhD, APRN, BC, and the International Myeloma
Foundation Nurse Leadership Board
About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased
osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood
clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an
essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can
significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone
disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise,
maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of
bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.
A
main feature of multiple myeloma (MM) is bone
destruction, and many patients will initially
present with pain related to osteolytic lesions or
vertebral compression fractures (Sezer, 2009).
Destructive bone lesions and diffuse osteopenia
are secondary to the stimulation of osteoclast-activating growth
factors, cytokine release, and the lack of osteoblastic response
(Esteve & Roodman, 2007). The clinical consequences of
osteolytic bone lesions—fractures, severe bone pain, spinal
cord compression, hypercalcemia, and renal insufficiency—can
be devastating for patients, negatively affecting immediate and
ongoing quality of life and worsening survival prospects (Kyle,
Gertz, et al., 2003).
At a Glance

Most patients with multiple myeloma will develop osteolytic
bone lesions. Pathologic fractures and other skeletal events
can result in poor circulation, blood clots, muscle wasting,
and decreased survival.

Supportive care targeting bone disease is an essential part
of myeloma therapy.

Oncology nurses play a key role in the management of
bone disease and maintenance of adequate bone health
throughout the course of myeloma.
Teresa S. Miceli, RN, BSN, OCN®, is the bone marrow transplant RN coordinator at the Mayo Clinic in Rochester, MN; Kathleen Colson, RN, BSN,
BS, is a clinical research nurse in the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, MA; Beth M. Faiman,
MSN, APRN-BC, AOCN®, is a nurse practitioner in the Hematology and Medical Oncology Department at the Cleveland Clinic in Ohio; Kena
Miller, RN, MSN, FNP, is a nurse practitioner in the Department of Medicine, Lymphoma/Myeloma Division, at Roswell Park Cancer Institute
in Buffalo, NY; and Joseph D. Tariman, PhD, APRN, BC, is an advanced practice nurse in the myeloma program at Northwestern University in
Chicago, IL. The authors take full responsibility for the content of this article. Publication of this supplement was made possible through
an unrestricted educational grant to the International Myeloma Foundation from Celgene Corp. and Millennium: The Takeda Oncology
Company. Colson is a consultant with Merck & Co., Inc., and Millennium: The Takeda Oncology Company; Faiman is a consultant and on the
speakers bureau at Celgene Corp. and Millennium: The Takeda Oncology Company; Miller is on the advisory board and speakers bureau at
Celgene Corp. and Millennium: The Takeda Oncology Company; and Tariman is a consultant with Millennium: The Takeda Oncology Company. The
content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial
bias. No financial relationships relevant to the content of this article have been disclosed by independent peer reviewers or editorial staff. (First
submission February 2011. Revision submitted March 30, 2011. Accepted for publication April 5, 2011.)
Digital Object Identifier: 10.1188/11.S1.CJON.9-23
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
9
Pathophysiology
of Myeloma Bone Disease
Bone disease is the major cause of morbidity and mortality
in patients with MM (Coleman, 2006). Osteolytic lesions
found with MM are caused by rapid bone turnover, which
occurs as a result of increased osteoclastic resorption that is
not accompanied by a comparable increase in bone formation
(Berenson, Rajdev, & Border, 2006; Epstein & Walker, 2006).
Normal bone formation is initiated by osteoblasts, and bone
resorption is initiated by osteoclasts. Osteoprotegerin is a
cytokine that inhibits production of osteoclasts. Osteoprotegerin
maintains the balance between bone resorption and formation.
Bone destruction in MM is believed to be multifactorial,
resulting from an interaction of bone marrow stromal cells and
myeloma tumor cells within the microenvironment of the bone
marrow (Coleman, 2001). Bone destruction is characterized
by overproduction of osteoclasts and reduced stimulation of
osteoblasts resulting in unbalanced bone turnover.
Bone pain and the incidence of pathologic fracture are high
among patients living with MM as a result of osteolytic bone
lesions and bone turnover related to excess cytokine levels.
Fractures typically occur near the time of diagnosis or relapse
and are pathologic in nature. The most common locations of
fracture are within the vertebral bodies (55%–70%), particularly
in the lumbar vertebral bodies, flat and long bones (including
the ribs), the extremities, and pelvis (Melton, Kyle, Achenbach,
Oberg, & Rajkumar, 2005).
Long-Term Effects of Bone Disease
As noted, the majority of patients with MM will experience
a pathologic fracture over the natural duration of their illness.
As a result, 80% of patients will experience pain and altered
quality of life (Roodman, 2008). The severity of bone disease
and number of lesions present at the time of the diagnosis help
to classify patients who are considered high risk. The Durie/
Salmon PLUS staging system has integrated the quantification
of bone lesions by magnetic resonance imaging (MRI) and
positron-emission tomography (PET) to better define the
treatment plan for patients newly diagnosed with early disease
(Durie, 2006). Two staging systems are used to standardize
treatment approaches. The International Staging System was
introduced in 2005 by the International Myeloma Working
Group and is based on two factors, serum beta-2 microglobulin
and serum albumin levels (Greipp et al., 2005). This system
divides cases of myeloma into three stages, providing a reliable
prognostic tool. The Durie-Salmon staging system (Durie &
Salmon, 1975) is based on the following criteria: percentage
of marrow involved by monoclonal plasma cells; level of
abnormal monoclonal immunoglobulin in the blood and/or
urine; and level of serum calcium, renal dysfunction, degree of
anemia, and presence of bone damage (CRAB) as later defined
by the International Myeloma Working Group (Kyle, Child, et
al., 2003). Although both systems provide valuable diagnostic
and prognostic information, neither system describes how the
severity of bone disease affects long-term outcomes.
10
The Durie/Salmon PLUS staging system (Durie, 2006)
assimilates imaging methods into a new generation of anatomic
and functional myeloma staging. Table 1 outlines the diagnostic
imaging commonly used for patients with MM. With the use of
MRI, whole body fluorodeoxyglucose (FDG) PET scanning and
whole body computed tomography (CT), combined with PET
directly or by fusion, the Durie-Salmon staging system has now
been enhanced to include anatomic and functional staging. The
new system may provide better classification of early disease.
The Durie/Salmon PLUS staging system provides the following
advantages.
• Assessment of cell mass
• More accurate staging for patients who lack traditional
biomarkers because of hyposecretory or nonsecretory disease
• Identifies patients at poor risk who have more than 20 focal
lesions and/or extramedullary disease
• Confirms stage I active disease for patients with negative x-rays
• Provides a more detailed discernment between those
diagnosed with stage II and III disease
The degree of bone involvement affects quality of life as well as
prognosis. Compromised skeletal structure because of lytic lesions
and vertebral compression fracture can result in altered mobility
and function; therefore, early detection can offer potential benefits
to patients. The life-altering mobility and functional aspects of
myeloma are further described in Rome, Jenkins, Lilleby, and the
International Myeloma Foundation Nurse Leadership Board (2011).
Assessment of Myeloma Bone Disease
Laboratory Testing
Laboratory tests to assess bone include calcium, vitamin D,
fractionated alkaline phosphatase, and creatinine. Hypercalcemia,
defined as a corrected serum calcium greater than 11.5 mg/dl, is
seen in 10%–15% of patients at presentation and is considered
Table 1. Diagnostic Imaging in Multiple Myeloma
DIAGNOSTIC IMAGING
PURPOSE
Bone density test
Useful in detecting osteopenia and osteoporosis
Bone scan
Not a useful tool in assessing myeloma bone
disease
Magnetic
resonance imaging
More sensitive than x-rays
Used when vertebral compression fracture
or spinal cord compression is suspected
Can detect edema and fluid surrounding
active vertebral bone disease and marrow
and soft tissue involvement
Positron-emission
tomography/computed
tomography
Useful in assessing presence of lytic bone lesions and detecting occult plasmacytomas
Skeletal survey
Skeletal x-rays used to detect lytic bone lesions and bone fractures
Also used in staging of multiple myeloma
Note. Based on information from Durie, 2006; Roodman, 2008.
August 2011 • Supplement to Volume 15, Number 4 • Clinical Journal of Oncology Nursing
an oncologic emergency. Alkaline phosphatase will be elevated
with a high bone fraction and can indicate an increased rate of
bone growth. Vitamin D levels can provide additional baseline
evaluation of bone health because vitamin D deficiency can
interrupt calcium metabolism, leading to weakened bones.
Adequate vitamin D is crucial in preventing bone loss (BischoffFerrari, 2007; Cashman, 2007; Guise, 2006; Mauck & Clarke,
2006; Roodman, 2004).
A variety of laboratory markers are used to monitor bone
resorption in patients with MM. These markers can predict the
development of new skeletal events. If the parathyroid hormone
(PTH) level is low, bones will release more calcium in the blood,
leading to hypercalcemia, and weakening of the bones, as well
as resulting in fractures and pain. Some common symptoms
of hypercalcemia include polyuria, polydipsia, constipation,
confusion, somnolence, fatigue, vomiting, dehydration, weakness,
and renal insufficiency. N-telopeptides are fragments of collagen
released by the bone during bone turnover. When bone is
broken down, this collagen is released in the urine; high levels
of N-telopeptides in the urine can be indicative of active bone
disease. Endocrine evaluation that includes thyroid, parathyroid,
and testosterone levels may be indicated throughout the course
(Bischoff-Ferrari, 2007; Cashman, 2007; Coleman, 2006; Guise,
2006; Mauck & Clarke, 2006; Roodman, 2004).
Skull (more
than 35% risk)
Mandible
(10% risk)
Humeri
(22% risk)
Spine (more
than 49% risk)
Pelvis
(34% risk)
Femora
(13% risk)
Diagnostic Imaging
Bone imaging is an important tool for diagnosis and monitoring bone disease in patients with myeloma. Patients often are
initially diagnosed because of the onset of acute bone pain or
pathologic fracture. Any bone may be affected in MM; the bones
with the highest chance of being affected are the spine with
more than a 49% risk, the skull with more than a 35% risk, the
pelvis at 34% risk, the humeri with 22% risk, the femora at 13%
risk, and the mandible at 10% (Roodman, 2008) (see Figure 1).
Of note, bone disease in myeloma is caused by an imbalance
of osteoblast and osteoclast activity causing bone destruction
and absence of bone formation. Therefore, bone scans are not
the imaging technique of choice because the degree of bone
disease may be underestimated (Roodman, 2008). A complete
skeletal survey, the standard method of imaging in patients with
MM, detects fractures, tumors, or degenerative changes in the
bone. Metastatic bone surveys show that skeletal abnormalities
are present in 79% of newly diagnosed patients. Osteosclerotic
lesions are rarely seen (Kyle, Gertz, et al., 2003).
Metastatic bone survey, the gold standard for assessing bone
disease in myeloma, is able to only identity the lytic disease
where a minimum of 30% of the trabecular bone has been
destroyed, which basically renders the method somewhat
insensitive. In addition, this technique does not demonstrate
response to therapy (Roodman, 2008). These limitations of the
skeletal survey have led to the use of three additional imaging
techniques: CT, PET, and MRI. These three are not considered
standard of care in the diagnosis of myeloma bone disease, but
can be helpful in discerning suspicious lesions or areas of focal
bone destruction. The more sensitive CT may reveal bone lesions
not seen on a metastatic bone survey, particularly for patients
who are experiencing pain. An MRI may reveal the presence
of bone marrow involvement or spinal cord compression. For
Figure 1. Bones at Highest Risk of Being Affected
by Multiple Myeloma
Note. Copyright 2011 by Bodell Communications, Inc./Phototake. All
rights reserved. Used with permission.
Note. Based on information from Roodman, 2008.
patients with nonsecretory or oligosecretory myeloma, MRI
may reveal the presence and progression of disease and provide
prognostic information as discussed in the Durie/Salmon PLUS
staging system. For patients with renal insufficiency, which
occurs in 20%–60% of patients throughout their disease, care
should be taken to avoid the use of gadolinium (Angtuaco, Fassas,
Walker, Sethi, & Barlogie, 2004; Kyle, Schreiman, McLeod, &
Beabout, 1985; Mariette et al., 1999; Tariman & Faiman, 2011;
Tryciecky, Gottschalk, & Ludema, 1997).
Although MRI has a higher sensitivity compared to a typical
radiograph in providing anatomic information about the bone
marrow, it lacks specificity because of the small signal strength
on T1- and T2-weighted images. MRI is the diagnostic tool of
choice for spinal cord compression. CT has a higher sensitivity
for smaller lesions and is useful in detecting extraosseous
extensions of the disease and to determine bone destruction.
PET scans are useful in detecting bone disease, bone marrow
infiltration, and extramedullary disease. Whole-body PET
scans are much more sensitive than x-rays and other diagnostic
imaging tools. The PET scan uses a radio-labeled sugar-based
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
11
tracer called 18F-fluorodeoxyglucose (18F-FDG) that identifies
metabolically active cells. FDG is absorbed but not metabolized
in the cells and, therefore, accumulates. Areas of malignancy
and infection are metabolically more active and typically
uptake the tracer at greater rates. This provides a mechanism
for imaging areas of infection or malignancy (Tryciecky et al.,
1997). The use of whole-body 18F-FDG PET, combined with
either CT alone or PET/CT, has been found to be useful in the
detection of residual disease for myeloma that has been treated
and is the imaging of choice for evaluation of extramedullary
disease (Bartel et al., 2009). However, critics warn that the PET/
CT tool requires additional study before it becomes part of the
standard of care in patients with MM for the following reasons
(Dimopoulos, Moulopoulos, & Terpos, 2009).
• PET/CT may miss small lytic lesions and diffuse spinal
involvement readily detected through use of an MRI.
• PET/CT have been known to provide “false-positive” results,
particularly in areas of inflammation and infection, postsurgical sites, and vertebroplasty or other metastatic disease.
• Reimbursement remains an issue.
Treatment of Myeloma Bone Disease
The management of MM-related bone disease involves
treatment of the disease itself, which controls the myeloma
and the underlying manifestations of the disease. The most
common forms of treatment are chemotherapy and autologous
stem cell transplantation (for eligible patients). For patients
with bone involvement who do not experience bone-related
pain, systemic therapy often is the primary treatment choice.
Adjuvant therapies include localized radiation, orthopedic
surgical interventions including kyphoplasty or vertebroplasty
for vertebral fractures, and the use of agents that can inhibit
bone resorption, such as bisphosphonates.
Novel Antimyeloma Agents
Novel agents used today in the treatment of MM may positively
affect bone metabolism. Management of active MM with
effective antimyeloma therapies will help to decrease the risk of
worsening bone structure and risk of fracture. However, these
therapies are far from perfect, and it now is clear that skeletal
disease may progress despite the achievement of stable disease
(Kanis & McCloskey, 2000).
The proteasome inhibitor bortezomib appears to have an
effect on myeloma bone disease. It inhibits nuclear factor kappa-B
(NF-kB) activity, a critical factor for osteoclast formation and
survival. It appears to act during the initial and ending stages of
osteoclast differentiation. Several clinical trials conducted with
bortezomib have demonstrated that it may increase osteoblast
activity, leading to new bone formation, as researchers have
reported an increase in bone formation markers in some patients
(Pennisi, Li, Ling, Khan, Zangari, & Yaccoby, 2009).
The novel agent thalidomide may halt receptor activator of
NF-kB ligand (RANKL)-induced osteoclast formation in vitro
(Terpos et al., 2008). Lenalidomide, an immunomodulatory drug
(IMiD) and an analog of thalidomide that is more active with an
improved side-effect profile, decreases osteoclast formation and
12
activity (Bolzoni et al., 2010; Breitkreutz et al., 2008; Terpos et
al., 2009). In vitro studies demonstrate that thalidomide and the
currently investigational immunomodulatory drug pomalidomide
can inhibit the osteoclast activation process (Bolzoni et al.,
2010). The effect of thalidomide combined with dexamethasone
reduces bone resorption (Roodman, 2008). The combination
of bortezomib, thalidomide, and dexamethasone reduces bone
resorption and the RANKL/osteoprotegerin ratio; however, no
impact on the formation of bones was observed (Terpos et al.,
2009). Whether combining lenalidomide with bortezomib would
enhance the osseous effects of each agent alone is unknown;
potentially this is a topic for future study. As the understanding
of myeloma bone biology develops, more targeted therapies have
the potential to emerge (Yeh & Berenson, 2006).
Bisphosphonates
Bisphosphonates are strong inhibitors of bone resorption
and are effective in the management of hypercalcemia of
malignancy, decrease risk of fractures, and may decrease pain
in some patients. Bisphosphonates bind to mineralized bone
throughout resorption as well as inhibit osteoclast maturation.
They cause osteoclast apoptosis as well as prevent attachment to
the bone. The bisphosphonates that generally are administered
to patients with MM in the United States include pamidronate
and zoledronic acid. Both are given via IV, but the time of
infusion differs for each. Skeletal-related events can be reduced
with bisphosphonates, which decrease bone complications and
improve quality of life (Fitch & Maxwell, 2008). It also has been
suggested that pamidronate has an antimyeloma effect (Terpos
& Dimopoulos, 2005); an antimyeloma effect has recently been
shown for zoledronic acid (Morgan et al., 2010).
Radiation
Myeloma cells have a high level of sensitivity to radiation,
and radiation to affected areas of bone is a useful management
modality for some patients with MM, providing local pain
and tumor control as well as preventing or treating skeletal
fractures. Radiation may be curative in patients with solitary
bone plasmacytomas (Yeh & Berenson, 2006). Unfortunately,
solitary bone plasmacytoma will evolve to MM in the majority
of patients within two to three years. Fortunately, about 15%–
45% of patients will remain disease free at 10 years following
diagnosis with an overall median survival of 7–12 years (Weber,
2005). Total body irradiation was used in the past to treat
MM but, because of its severe toxicities and modest benefit,
this treatment modality is rarely used today (Hu & Yahalom,
2000). The use of radiation should be limited as it may cause
permanent bone marrow damage in the treatment areas
and compromise organ function within the treatment fields
(National Comprehensive Cancer Network, 2010; Roodman,
2008; Yeh & Berenson, 2006).
Surgical Procedures
A large lytic lesion that is present but has not yet progressed
to a pathologic fracture may require stabilization to prevent
a fracture. A surgical procedure may become a necessity to
decrease the size of the tumor, control pain, and prevent or treat
August 2011 • Supplement to Volume 15, Number 4 • Clinical Journal of Oncology Nursing
fractures. The spine, long bones, and pelvis are the most common
areas affected. Patients with tumors affecting the long bones or
weight-bearing joints may benefit from prophylactic surgery to
stabilize and restore function to the affected bone. Intramedullary
rod placement in the femur or pins and screws may be used for
surgical fixation if the bone quality is good enough to support
such hardware. Open surgical repairs, despite the invasiveness of
these procedures, may be considered even at an advanced stage of
disease to prevent impending fracture (Cady, Easson, Aboulafia,
& Ferson, 2005). Stabilizing bone before a fracture occurs is far
easier, and doing so will result in less pain and morbidity (Awan,
Azer, Harrani, & Cogley, 2002).
Vertebral compression fractures are common among patients
with MM. Two additional surgical techniques specific to the spine
include percutaneous vertebroplasty and balloon kyphoplasty.
Both are minimally invasive procedures and are performed on
an outpatient basis by an interventional radiologist, orthopedic
surgeon, or a neurosurgeon. Both procedures involve using
contrast guided-imaging under CT or CT fluoroscopy and an
incision of less than 1 cm to reach the anterior and paramedian
aspect of the vertebral body. In vertebroplasty, a hollow needle
is passed through the skin into the fractured vertebra and bone
cement (polymethylmethacrylate) is injected through the hollow
needle into the compressed or fractured area. Kyphoplasty is
similar to verteboplasty, but a balloon tamp is inserted into the
fractured vertebral body, which then is inflated in an attempt
to restore vertebral height. The balloon is then deflated and
withdrawn, forming a cavity in the vertebral body; the cavity
is then filled with bone cement. Using balloon kyphoplasty
instead of vertebroplasty can decrease the chance of cement
extravasation; vertebroplasty does not involve restoring the
structure of the collapsed vertebral body and requires a highpressure cement fill that can lead to leakage (Roodman, 2008).
Both procedures can provide immediate pain relief in some
patients along with improvements in functional stability and
spine stabilization. A recent randomized, controlled, open-label
trial compared balloon kyphoplasty with usual nonsurgical care
in patients with cancer, including patients with MM, who had
vertebral compression fractures. Patients receiving kyphoplasty
had improved back-specific physical function, more rapid
back pain relief, and improved quality of life. Potential serious
complications include cement leakage (Berenson et al., 2011). The
risk for future fractured vertebral bodies rises in those opting for
vertebroplasty or kyphoplasty as compared with individuals not
undergoing either procedure (Ludwig & Zojer, 2007).
Emerging Treatments
RANKL is required for production and survival of osteoclasts
and appears to play a role in the process of bone destruction
(Roodman, 2008). The human monoclonal antibody denosumab
binds to RANKL, preventing it from activating its receptor,
RANK, thereby blocking its effects. Denosumab is approved for
use in preventing skeletal-related events in solid tumors and is
indicated for the management of postmenopausal osteoporosis
in women at increased risk for fractures. Denosumab is not
approved in the United States for administration to patients
with MM, although it currently is used in clinical trials, as are
Dickkopf-related protein 1 (DKK1) inhibitors. DKK1 and other
members of the Wnt signaling pathway are logical therapeutic
targets (Roodman, 2008).
Risk Factors Adversely
Affecting Bone Health
In addition to the diagnosis of MM, patients can have
comorbid conditions that may place them at risk for poor
bone health, such as osteoporosis, metastatic malignancies,
immobility, side effects from long-term steroid and other drug
use, and hormone changes. Factors contributing to osteoporosis
include renal disease, natural or therapy-induced gonadal
failure, depression, diabetes, and vitamin deficiencies (Mauck
& Clarke, 2006; Mezuk, Eaton, & Golden, 2008).
Osteoporosis and Risk of Fracture
Risk factors for osteoporosis are numerous and can be
classified as primary or secondary (Mauck & Clarke, 2006) (see
Table 2). Primary causes are those that cannot be modified
(Cashman, 2007), and include female gender, increased age,
family history of osteoporosis or fracture, small or thin frame,
and low levels of sex hormones (Mauck & Clarke, 2006).
Secondary causes are potentially modifiable through medical
intervention and behavioral changes; they include nutritional
deficits, chronic medical conditions, inactivity, smoking,
alcohol abuse, and certain medications (Cashman, 2007;
Mauck & Clarke, 2006). Thirty to 60% of men experience
osteoporosis related to decreased gonadal function, use of
glucocorticosteroids, and alcoholism; 50% of women will
experience osteoporosis related to primary and secondary risk
factors such as decreased estrogen, glucocorticosteroid use, and
hyperthyroidism (Mauck & Clarke, 2006).
Table 2. Risk Factors Contributing to Bone Loss,
Osteoporosis, and Risk of Fracture
CATEGORY
RISK FACTORS
Primary risk
factors
Older than age 50 for men and women, female gender,
postmenopausal at any age, men with lower testosterone and estrogen levels, personal and first-degree relative with a history of fracture as an adult, dementia, and
ethnicity (Caucasians and Asian Americans have a higher
incidence than Hispanics and African Americans.a)
Secondary
risk factors
Low body weight (less than 127 lbs.), smoking, certain
medications, hypogonadism (hormone deficiency and
being younger than age 45), comorbid conditions, poor
health and frailty, recent falls, inactivity and immobility
(i.e., prolonged bed rest or wheelchair bound), and diet
(more than two alcoholic drinks per day, low calcium intake, vitamin D deficiency of any cause, and excess consumption of vitamin A, caffeine, sodium, and protein)
Difference in ethnic prevalence may be related to underreporting in
some ethnic groups.
Note. Based on information from Adami, 2009; Cashman, 2007; Everitt,
et al., 2006; Guise, 2006; Mezuk, Eaton, & Golden, 2008; Mezuk,
Eaton, Golden, Wand, et al., 2008; Mauck & Clarke, 2006; National
Osteoporosis Foundation, 2010; Szulc et al., 2008; Wick, 2009.
a
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
13
About 55% of the U.S. population older than age 50 is at
high risk for the development of osteoporosis. An estimated 10
million individuals are affected by the disease, with more than
34 million at risk as evidenced by low bone mass. Osteoporosis
is a chronic and progressive disease characterized by decreased
bone mass, leading to structural changes within the bone,
placing an individual at a higher risk for developing a fracture,
particularity of the spine, wrist, or hip. Osteoporosis affects four
times as many women as it does men, with significant risk seen
among all ethnic backgrounds (Mauck & Clarke, 2006).
The National Osteoporosis Foundation ([NOF], 2010)
estimates that 80% of women and 20% of men older than age
50 are affected by osteoporosis. In addition, one in two women
and one in four men will experience a fracture secondary to
osteoporosis. Studies have shown that not only does the risk
for subsequent fractures increase after the first event, but
the quality of life and impact on independent activities of
daily living is dramatically reduced following a fracture (NOF,
2010). The median age for diagnosis of MM is 66 years (Kyle &
Rajkumar, 2007). MM and other comorbid conditions (see Figure
2) increase the risk of age-related osteoporosis and fracture.
Malignancy
(e.g., multiple
myeloma,
amyloidosis)
Endocrine disorders
(e.g., Cushing syndrome,
hypogonadism,
hyperthyroidism, primary
hyperparathyroidism,
diabetes)
Gastrointestinal disease
(e.g., chronic liver diseasea,
inflammatory bowel diseaseb,
celiac disease, gastric
bypass or gastrectomy)
AIDS
and HIV
Rheumatologic disorders
(e.g., rheumatoid arthritis,
systemic lupus erythematosus,
ankylosing spondylitis,
juvenile polyarticular
arthritis)
Renal insufficiency
or failure (renal
osteodystrophy)
Anorexia nervosa,
malnutrition, alcoholism,
depression, and coronary
artery disease
a
b
Mobility disorders
(e.g., Parkinson disease,
chronic obstructive
pulmonary disease, cerebrovascular
accident, multiple
sclerosis, peripheral
neuropathy, cerebral palsy)
Particularly primary biliary cirrhosis and primary sclerosing cholangitis
Crohn’s disease
Figure 2. Comorbid Conditions Associated With
Osteoporosis
Note. Based on information from Adami, 2009; Everitt et al., 2006; Mauck
& Clarke, 2006; Mezuk, Eaton, & Golden, 2008; Mezuk, Eaton, Golden,
Wand, et al., 2008; Szulc et al., 2008)
14
Other Comorbid Conditions
Renal osteodystrophy: Bone loss associated with chronic
renal disease is one of the most common osseous complications of
patients with MM. The bone changes from chronic kidney disease
or renal osteodystrophy can begin in adults several years prior
to the appearance of any symptoms. Management of myelomarelated renal complications are described in Faiman, Mangan,
Spong, Tariman, and the International Myeloma Foundation
Nurse Leadership Board (2011). Patients with either osteoporosis
or renal osteodystrophy experience increased risk of fractures
and resultant joint and bone pain, but renal osteodystrophy does
not necessarily respond to bisphosphonates (Legg, 2005).
Kidneys have a significant role in the maintenance of
bone mass throughout one’s life by maintaining calcium and
phosphorus levels in the blood. Patients with kidney disease
may develop hypocalcemia leading to increased stimulation of
the parathyroid glands to release PTH. The excess PTH results
in osteopenia, and constant removal of calcium over time will
weaken the bones (Legg, 2005).
The kidneys also regulate serum calcium by producing
calcitriol, a form of vitamin D produced by healthy kidneys that
helps the body absorb dietary calcium. In kidney failure, calcitriol
production is decreased and the resulting hypocalcemia stimulates
the parathyroid gland to release more PTH, which contributes to
further osseous calcium loss. Nurses need to be aware that routine
monitoring for serum PTH and vitamin D should take place in
patients with chronic kidney disease (Legg, 2005).
Gonadal insufficiency: Gonadal failure can be a natural
part of aging or therapy related and can affect both men
and women. Postmenopausal women have a higher risk of
developing osteoporosis and risk of fracture. The loss of
estrogen results in a higher rate of bone loss (Everitt et al.,
2006). Bone mineral density (BMD) in women is estimated to
decrease at over 2% annually for the first five years following
menopause, and then the rate slows, whereas the rate of bone
loss in men begins in midlife and is further reduced from 0.5%–
1% per year (Guise, 2006). Selected therapies, both surgical and
medical, that result in gonad failure and contribute to the risk of
osteoporosis and risk of fracture are listed in Table 3.
Depression: Major depressive disorders occur in about
16% of the general population, but more frequently in those
diagnosed with cancer (Mezuk, Eaton, & Golden, 2008; Mezuk,
Eaton, Golden, Wand, & Lee, 2008). People who suffer from
major depressive disorders have a lower BMD than those in
control groups. The association of depression, osteoporosis,
and risk of fracture is unclear. Physiologically, hormone levels
that promote osteoclastic function and decrease osteoblastic
function, including interleukin-6, tumor necrosis factor-alpha,
PTH, C-reactive protein, and cortisol, also are elevated in those
who have major depressive disorders. Secondary risk factors
may play the greatest role because an association exists between
depression and unhealthy behaviors (e.g., smoking, alcohol use,
fatigue resulting in inactivity) (Mezuk, Eaton, & Golden, 2008).
Diabetes: People suffering from type 1 diabetes have
decreased BMD and increased risk of fracture, and those with
type 2 diabetes also are at a higher risk for suffering a fracture
even if their BMD is normal or increased (Adami, 2009).
However, the mechanism for bone loss in these patients is
August 2011 • Supplement to Volume 15, Number 4 • Clinical Journal of Oncology Nursing
Table 3. Bone Loss and Cancer Therapy
THERAPY
risk of fracture than previous use and may be age- and life-stage
dependent (Mezuk, Eaton, & Golden, 2008).
TUMOR
Chemotherapy (cyclophosphamide,
methotrexate or ifosfamide, and
alkylating agents)
Various malignancies (e.g.,
breast cancer, multiple myeloma,
osteosarcoma, Hodgkin or nonHodgkin lymphoma)
Glucocorticoids
Various malignancies and
autoimmune disorders
Hormone therapy (androgendeprivation therapy, selective
estrogen-receptor modulators,
and aromatase inhibitors)
Prostate, testicular, ovarian, and
breast cancer
Radiation therapy
Various malignancies
Stem cell transplantation
Various malignancies
Surgical (bilateral orchiectomy
and oophorectomy)
Prostate, testicular, ovarian, and
breast cancer
Note. From “Bone Loss and Fracture Risk Associated With Cancer
Therapy,” by T.A. Guise, 2006, Oncologist, 11, p. 1122. Copyright 2006
by AlphaMed Press. Adapted with permission.
not well understood (Chau & Edelman, 2002). Patients with
MM undergoing treatment with high-dose steroids have an
increased risk of developing steroid-induced diabetes which,
in turn, increases the risk of osteoporosis (Faiman, Bilotti,
Mangan, Rogers, & the International Myeloma Foundation Nurse
Leadership Board, 2008).
Cardiovascular disease: The association of osteoporosis
and cardiovascular disease in men is not well understood and
may be a culmination of comorbid conditions that place a person
at risk for both conditions (e.g., inactivity, low testosterone
levels, end-stage renal disease) (Szulc, Kiel, & Delmas, 2008).
Medications
Many cancer treatment regimens can have adverse effects
on bones, resulting in more rapid and severe bone loss than
seen in primary causes of osteoporosis in men and women
(Guise, 2006; Melton et al., 2005). In addition, many comorbid
conditions are treated with pharmacotherapy, which also may
contribute to osteoporosis and risk of fracture. Figure 3 lists
drugs that may predispose patients to osteoporosis, putting
them at a higher risk for fracture.
Steroids: Glucocorticoids (dexamethasone or prednisone)
remain a backbone of antimyeloma therapy. Steroids kill
myeloma cells directly and may enhance the efficacy of other
myeloma drugs when used in combination. However, steroid
use may result in osteopenia or osteoporosis by inhibiting or
killing osteoblasts, stimulating bone resorption, inhibiting
calcium absorption, and increasing calcium excretion. Steroid
use also is associated with avascular necrosis or osteonecrosis
(Faiman et al., 2008).
Antidepressants: Antidepressant medications such
as selective serotonin reuptake inhibitors and tricyclic
antidepressants have been implicated in increased risk of
fractures. Current use of antidepressants plays a greater role in
Bone Marrow Transplantation
Multiple small studies evaluating BMD following autologous
and allogeneic bone marrow transplantation report that
bone loss is a common side effect. Few long-term studies are
available, but disturbance in bone metabolism and reduced
BMD is measurable years after the procedure. The mechanism
is not completely understood, however, alteration of the
osteoprotegerin/RANKL system may play a significant role
(Ebeling et al., 1999; Kang et al., 2000; Kerschan-Schindl
et al., 2004; Lee, Cho, et al., 2002, Lee, Kang, et al., 2002).
Interestingly, one small study (Kielholz et al., 1997) of 29
patients who underwent autologous bone marrow or peripheral
blood transplantation following high-dose chemotherapy
showed that they did not have significant osteopenia despite
high-dose steroids, prolonged inactivity, and decreased
estrogen levels. The lowest BMD was seen in men who had
the lowest testosterone levels. Because this was a follow-up
study of patients who were five years post-transplantation,
these unexpected results may be from recovery of endocrine
function during that time. With such a small cohort of patients,
however, additional investigation is warranted before making
any conclusions (Kielholz et al., 1997).
Diet
Although diet is considered a secondary risk factor for
osteoporosis and risk of fracture, the peak bone mass, which
is reached in youth, is not modifiable in adults. About 90%
of bone mass is established within the first two decades of
life and, most significantly, during puberty (Cashman, 2007).
Vitamins and nutrients important for bone mineralization
and skeletal development are listed in Table 4. Vitamin D and
calcium are required during development and throughout
life to promote bone health (Everitt et al., 2006). Maximizing
serum vitamin D levels, as measured by 25-hydroxyvitamin D
(25-OHD), contributes to an increase in BMD and is associated
with improved muscle strength, resulting in a 20% decreased
3Anticonvulsants (phenytoin or phenobarbital)
3Cytotoxic drugs and immunosuppressants (cyclosporine A,
tacrolimus)
3Drugs causing hypogonadism (aromatase inhibitors, methotrexate,
antimetabolite chemotherapy, depomedroxyprogesterone acetate,
and gonadotropin-releasing hormone agonists such as buserelin,
leuprolide, and nafarelin)
3Drugs causing sedation or confusion (pain medication, sleep aids,
antianxiety drugs, or antihistamines)
3Glucocorticoid excess (current or previous use for more than three
months)
3Heparin (long-term), lithium or aluminum, and l-thyroxine overreplacement
Figure 3. Checklist of Drugs Associated With
Osteoporosis and Risk of Fracture
Note. Based on information from Guise, 2006; Mauck & Clarke, 2006.
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
15
Table 4. Factors That Reduce Osteoporosis
and Risk of Fracture
INTERVENTION
ITEMS
Diet or dietary
supplements
Calcium, copper, magnesium, phytoestrogens,
vitamin C (with caveats about potential
interaction with bortezomib), vitamin D,
vitamin K, and zinc
Pharmacotherapy
Estrogen, statins, and thiazides
Weight-bearing
activity
–
Note. Based on information from Adami, 2009; Mauck & Clarke, 2006;
Mezuk, Eaton, & Golden, 2008; Mezuk, Eaton, Golden, Wand, et al., 2008.
risk of fracture in older adults. Bischoff-Ferrari (2007) stated
that optimal levels of serum 25-OHD are between 90 and 100
nmol/L. Inadequate levels of vitamin D cause elevation of
PTH that can lead to decreased BMD (Bischoff-Ferrari, 2007;
Mauck & Clarke, 2006). Evidence shows that increased levels
of vitamin K reduce the risk of fracture. Phytoestrogens, found
naturally in plant-based products such as soy, are a nonsteroidal
compound that may act as a safe hormone replacement therapy
for postmenopausal women (Cashman, 2007). Smoking and use
of alcohol (more than two drinks per day) are both associated
with decreased bone cell proliferation related to impaired
absorption of calcium in the intestine (Mauck & Clarke, 2006;
Mezuk, Eaton, Golden, Wand, et al., 2008). Consumption
of excess or insufficient amounts of protein, vitamin A, and
phosphorus can have positive or negative effects on bone
health, depending on their renal effects. Paradoxically, obesity
has a positive effect on BMD (Cashman, 2007; Everitt et al.,
2006), even in those patients considered to be inactive. Weightbearing activity promotes bone density, so the additional body
mass contributes to bone strength (Everitt et al., 2006; Mauck
& Clarke, 2006; Mezuk, Eaton, & Golden, 2008). However,
the comorbid conditions associated with obesity make this a
counterproductive approach to promoting bone health.
MM occurs more frequently in African Americans than in
other racial or ethnic groups (Kyle & Rajkumar, 2007). African
Americans have lower serum levels of vitamin D, which may
place individuals at increased risk of fracture. Although the risk
of falling is similar to Caucasians, the risk of fracture is lower.
This process is not fully understood, but possible elements
protecting African Americans include increased rates of obesity,
bone composition, remodeling, and inherited factors (Aloia,
2008).
Evidence-Based Recommendations
to Manage and Maintain Bone Health
Comorbidities and concomitant risk factors, such as age,
gender, medications, and mobility, should be considered when
developing a treatment plan and will influence the approach
taken for each patient (see Figure 4). In addition to mobility
and exercise, which are discussed in depth in another article
16
in this supplement (Rome et al., 2011), nurses can assist
patients to manage their bone health by maintaining proper
diet and nutrition, undergoing radiation treatment or surgical
procedures when necessary, and safely taking bisphosphonates
and pain medications where appropriate.
Diet and Supplements
Only general recommendations exist in regard to diet,
supplements, and bone health in MM. Clinicians should
encourage patients to eat well-balanced diets comprising
fruits, vegetables, protein, and carbohydrates. Most nutritional
supplements are safe in moderation; however, based on
preclinical evidence, the Nurse Leadership Board suggests the
following compounds be used with caution by patients receiving
bortezomib. Vitamin C interferes with the ability of bortezomib
to kill human cancer cell lines in culture, apparently by binding
to bortezomib and inactivating it (Zou et al., 2006). Alpha
lipoic acid, often recommended for the treatment of peripheral
neuropathy, has been shown to interfere with antimyeloma
effects of bortezomib in myeloma cell lines (Steinberg et al.,
2009). In addition, preclinical (in vitro and in vivo) research
demonstrated tumor cell death caused by bortezomib may be
negated by the use of green tea (Golden et al., 2009). Although
additional research is warranted, and no clinical evidence
exists, the International Myeloma Foundation Nurse Leadership
Board recommends avoidance of vitamin C, alpha lipoic acid,
and green tea on the day of bortezomib therapy.
Calcium and vitamin D supplementation is advised for
all patients with osteopenia or osteoporosis, particularly if
they are receiving bisphosphonates such as pamidronate or
zoledronic acid. The NOF’s recommendations for calcium and
vitamin D supplementation are provided at http://nof.org/
aboutosteoporosis/prevention/calcium.
In summary, for people older than age 50, 1,200 mg of calcium
and 800–1,000 IU of vitamin D daily are recommended. Those
younger than age 50 do no require as much, with 1,000 mg
of calcium and 400–800 IU of vitamin D daily recommended.
Of note, however, individuals with hypercalcemia or renal
insufficiency should not take calcium replacement (NOF,
2010), both of which may be concerns for patients with MM. A
discussion with a healthcare provider should take place.
Radiation as Treatment for Bone Disease
Care of patients receiving radiation for local pain and tumor
control includes alleviating side effects related to the radiated
field. The potential for side effects is dose dependent. External
beam doses can range from 600–800 cGy hemi-body irradiation
for palliation of generalized pain, 3,000 cGy for a localized painful
bone lesion, and to 4,500 cGy for tumor control. Patients receiving
lower-dose radiation for pain palliation have less potential for
side effects, but all should be monitored closely (Terpos &
Dimopoulos, 2005). For example, patients with head and neck
radiation may have trouble eating and swallowing and may
experience mouth sores. For these patients, good oral hygiene
is necessary to prevent mouth sores and decrease the risk of
infections. Pain medication may be indicated if severe mouth sores
or radiation burns to the skin develop. Individuals who receive
mediastinal, thoracic, or lumbar spine radiation may develop
August 2011 • Supplement to Volume 15, Number 4 • Clinical Journal of Oncology Nursing
Patient name:
Myeloma diagnosis:
Ig (G, A, M, E, or D); light chain
Date of diagnosis:
Renal involvement
Yes
If yes, serum creatinine is or glomerular filtration rate is
(kappa or lambda).
No
and creatinine clearance
ml per minute.
Bone involvement
Yes
No
Bone strengthening (bisphosphonate) medication(s) used:
Pamidronate (First dose:
Last dose:
Frequency:
Zoledronate (First dose:
Last dose:
Frequency:
Other:
(First dose:
Last dose:
Frequency:
)
)
)
Situations that require immediate medical attention include: Sudden onset of pain (may indicate a new fracture); back pain with sudden
change in sensation in lower or upper extremities or loss of bowel or bladder control (may indicate spinal nerve damage); noticeable changes in
mental status such as increased somnolence, confusion, or irritability; or severe constipation, nausea or vomiting, and excessive thirst and urination.
Guides for monitoring and maintaining bone health: Include blood tests and radiologic imaging; bone health is maintained with medications,
supplements, and physical activity; and pain management is important for maintaining physical activity and improving quality of life.
Medical Follow-Up
Blood and laboratory tests
(assessment of myeloma
activity)
Monthly while on therapy to assess response, then at discretion of clinician. Follow-up every three months, even
for stable disease. The National Comprehensive Cancer Network (NCCN) provides guidelines for testing, including
calcium and creatinine.
Bone health–monitoring
laboratory tests
Vitamin D and fractionated alkaline phosphate. Hormone levels such as parathyroid and thyroid hormone;
testosterone for men; and estradiol, follicle-stimulating, and luteinizing hormone for women.
Radiology and imaging
Bone survey should be performed annually or with new onset of pain or fracture to monitor for new bone lesions.
Bone density tests should be performed if other risk factors are present for osteoporosis. Magnetic resonance image,
positron-emission tomography, and computed tomography should be conducted at healthcare provider’s discretion.
Medications and Supplements
Bisphosphonates
Very good partial response (VGPR) or better, take monthly for one year; for less than VGPR, take monthly for two
years. Stop during remission; restart at relapse.
Calcium supplements
Younger than age 50, use about 1,000 mg per day; for those 50 and older or postmenopausal, use 1,200 mg per day.
Calcium supplements should not be used if blood calcium is elevated or kidney function decreased. Consult with an
endocrinologist.
Systemic treatment
For treatment of active disease, maintenance, and disease progression. Treatment options vary and schedule is
dependent on regimen prescribed.
Vitamin D supplements
Younger than age 50, use 400–800 IU per day; for those 50 and older, use 800–1,000 IU per day. Need for additional
supplementation is based on blood levels. Consult with an endocrinologist.
Pain Management
Balloon kyphoplasty
or vertebroplasty
Painful spinal fractures as a result of osteoporosis or multiple myeloma. May be conducted at the time of a fracture or to
prevent further compromise with worsening fractures. Evaluations by orthopedists or spine specialist may be needed.
Medications
Pain medications are variable. The World Health Organization provides guidelines for management. Consider
evaluations by orthopedists, physical therapists, or pain management clinic professionals.
Radiation
Should be prescribed for curative intent (palliative to control pain and decrease tumor size). Radiation should be used
with caution because it may lead to bone marrow fibrosis and scarring. Coordinate with the radiation oncologist.
Surgical fixation
Treat impending or actual fracture. Consult with orthopedists.
Self-Care and Health Maintenance
Exercise and activity
At diagnosis, conduct a baseline safety evaluation. Weight-bearing activity promotes bone strength. Consultation
with a physical medicine or spine specialist may be recommended to determine activity allowance.
Nutrition and hydration
Counsel patients on importance of maintaining a balanced diet and adequate fluid intake. Excess weight can worsen
bone pain and muscle fatigue, poor diet can worsen fatigue, and dehydration can worsen fatigue and cause renal
dysfunction. Consult with a nutritionist.
Oral hygiene and dental
care
Counsel good oral hygiene and have dental checkups every six months. Avoid invasive dental work if possible. If
needed, antibiotics may be prescribed prior to invasive dental procedure. Remind patients to inform their dentist
about the use of a bone-strengthening medication.
Figure 4. Long-Term Survivor Bone Health Plan for Clinicians Treating Patients With Multiple Myeloma
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
17
nausea, loss of appetite, or vomiting. Assessment of hydration and
calorie counts and evaluation by a dietitian may be necessary if
intake is compromised. All patients receiving cumulative external
beam radiation therapy may be at risk for radiation dermatitis and
are encouraged to keep their skin well hydrated with nonalcohol
lotions applied after radiation (Berkey, 2010).
Other common side effects of radiation include fatigue
and pain. Patients should be made aware of fatigue as a side
effect and be educated about managing their activities. Pain
medication may be warranted because individuals are required
to remain in an uncomfortable position during the radiation
treatment. Opioid or nonopioid analgesics may enhance comfort
during and after radiation treatment. A baseline and ongoing
pain assessment is integral to the patient’s plan of care.
Vertebroplasty or Kyphoplasty
Several studies suggest balloon kyphoplasty and vertebroplasty
are effective in reducing pain scores associated with vertebral
compression fracture, but each procedure has associated risks.
Potential risk is related to the cement injection resulting in
extravasation and causing nerve damage or other neurologic
issues. General risks include those associated with any surgical
procedure, namely increased risk of bleeding and infection.
Although minimal blood loss occurs with vertebroplasty
and balloon kyphoplasty, this risk increases if patients are
thrombocytopenic or are receiving low molecular weight
heparin, heparin, warfarin, or antiplatelet agents, aspirin, or
nonsteroidal anti-inflammatory drugs (NSAIDs). Although
specific recommendations are not documented, practices
followed by Nurse Leadership Board members at their institutions
include stopping aspirin and NSAIDs seven days prior to the
procedure. Management should be patient specific. Therapeutic
anticoagulation should be bridged from warfarin to low molecular
weight heparin or heparin, and this should be stopped within six
hours of the procedure. Baseline complete blood count, including
platelets, white blood count differential, and coagulation studies
such as prothrombin time, international normalized ratio, and
partial thromboplastin time may be indicated.
Infection risk could rise because of a low white blood cell
count as a result of marrow infiltration by myeloma or as a result
of the treatment itself. Clinicians should assess complete blood
count with white blood cell differential if patients are receiving
myelosuppressive antimyeloma treatment.
Mobility and exercise can be encouraged almost immediately
after the procedure. The cement used creates an internal cast
that hardens within minutes. Patients can resume their usual
activities and, if this procedure proves effective at decreasing
pain, patients can be weaned off pain medications gradually.
The use of slings and orthotic braces are not usually encouraged
unless used in preparation for planned surgical intervention
because they may reduce mobility and lead to osteopenia
(Tariman & Estrella, 2005).
the risk of skeletal-related events, but the optimal duration
of bisphosphonates therapy is unknown (Durie et al., 2007).
In patients achieving very good partial response or better
from their initial treatment as defined as greater than a 90%
reduction in serum or urine paraprotein, bisphosphonates
should be given on a monthly basis for one year. Although
clear evidence does not exist for modified administration, the
International Myeloma Working Group members have agreed
that patients should continue bisphosphonates use if they have
active bone disease or achieve less than a very good partial
response to treatment. If, after two years, the patient does not
have evidence of active bone disease, bisphosphonate use may
be discontinued. Bisphosphonates should be resumed at the
time of relapse if they were discontinued (Durie et al., 2007;
Kyle et al., 2007).
Although the aim is to reduce skeletal-related events, bisphosphonates can have adverse effects. Side effects of bisphosphonates include acute phase reactions, a small but increased
risk of osteonecrosis of the jaw (ONJ), and renal impairment
(Maxwell, Swift, Goode, Doane, & Rogers, 2003). Acute phase
reactions present as flu-like symptoms after the bisphosphonate infusion. These symptoms can be decreased with the use
of acetaminophen. Other side effects include nausea, fatigue,
and bone pain.
Monitoring and surveillance for ONJ is necessary. ONJ is
an uncommon but serious condition usually involving the
maxilla or mandible that may occur with prolonged use of
bisphosphonates. The incidence is relatively low, at 2%–10%.
Signs of ONJ may include jaw or tooth pain, and exposed bone
may be identified on physical examination. If ONJ symptoms
occur, initial treatment should be with antibiotic therapy and
not surgical procedures (Cafro et al., 2008). ONJ is thought to
be an infectious process, and the use of antibiotic prophylaxis
for dental procedures has been studied. The Italian Myeloma
Group evaluated patients receiving either amoxicillin-clavulanate
2 g per day by mouth, levofloxacin 500 mg per day by mouth,
beginning a day prior, up to three days after a dental procedure,
or standard care (no antibiotics). In patients receiving antibiotic
prophylaxis with amoxicillin-clavulanate, a decreased incidence
of infection with dental procedures such as cleaning, implants,
and extractions was noted. More studies are required to validate
these findings (Montefusco et al., 2008).
Prevention of ONJ is important, and good dental hygiene is
integral to the prevention of ONJ in patients with MM. Patients
should receive baseline and routine dental examinations every
six months. In addition, dentures should fit well because poorfitting dentures increase the risk of ONJ (Vahtsevanos et al.,
2009). Patients should advise their dental care providers when
they are receiving bisphosphonates.
Renal impairment is common in patients with MM. Precautions
concerning the use of bisphosphonates in patients with renal
impairment are discussed in Faiman et al. (2011).
Bisphosphonates
Pain Management
Bisphosphonates should be administered monthly for a
total duration of two years in individuals with lytic lesions
or osteoporosis. The International Myeloma Working Group
suggests that using pamidronate or zoledronic acid decreases
Damage to bones as a result of MM often causes pain; effective
doses of analgesia should be administered for patient comfort
and to increase mobility and quality of life. A good pain history
is essential to assessing the quality and character of a patient’s
18
August 2011 • Supplement to Volume 15, Number 4 • Clinical Journal of Oncology Nursing
Patient Tear-Out Tool
Long-Term Survivor Bone Health Plan for Patients
Patient name:
Multiple myeloma is treated as a chronic disease and management extends over time. It is important that you keep a history of your general myeloma
information and information specific to bone involvement and treatment. Bone health and kidney health are closely related, so it also is important that
you are aware of your kidney function. You are your own best advocate.
My myeloma diagnosis:
Ig (G, A, M, E, or D); light chain
(kappa or lambda).
Date of diagnosis:
My kidneys are affected
Yes
No
If yes, my creatinine is
and creatinine clearance
or glomerular filtration rate is
ml per minute.
My bones are affected
Yes
No
Bone strengthening (bisphosphonate) medication(s) used:
Pamidronate (First dose:
Last dose:
Frequency:
Zoledronate (First dose:
Last dose:
Frequency:
Other:
(First dose:
Last dose:
Frequency:
)
)
)
Symptoms that require immediate medical attention include:
• Sudden onset of pain (may indicate a new fracture)
• Back pain with sudden change in sensation in lower or upper extremities or loss of bowel or bladder control (may indicate spinal nerve damage)
• Noticeable changes in mental status such as increased somnolence, confusion, or irritability; or severe constipation, nausea or vomiting,
excessive thirst, and urination (may indicate increased calcium in blood)
The following guidelines will help monitor and maintain your bone health, including blood tests and radiographic imaging. Bone health is maintained with
medications, supplements, and physical activity. Pain management is important for maintaining physical activity and improving quality of life.
Medical Follow-Up
Blood and laboratory tests (performed at least
annually)
Last date tested:
Calcium, vitamin D, alkaline phosphate, and creatinine. Hormone levels such as
parathyroid and thyroid; testosterone for men; and estradiol, follicle-stimulating, and
luteinizing hormone for women
Radiology and imaging (performed annually and with
new onset of pain or fracture)
Last date tested:
Bone survey to monitor for new bone lesions and bone density to monitor for
osteoporosis. Magnetic resonance imaging, positron-emission tomography, and
computed tomography performed as recommended by the healthcare provider
Medications and Supplements
Bisphosphonates: If your disease status is very good
partial response rate (VGPR) or better, monthly use for
one year is recommended. If your disease status is less
than VGPR, monthly use for two years is recommended.
Used to increase bone strength and may have antimyeloma benefit. Stop during
remission or use as maintenance every three months. These guidelines continue to be
reviewed and may be revised over time.
Pain medication: Monitor changes in your pain, such
as an increase or decrease based on a pain scale of 1
(least pain) to 10 (worst pain).
Report any change in pain level. Use pain medication as prescribed by your healthcare
provider. Discuss other pain management techniques if your pain is not well controlled
with medication (i.e., balloon kyphoplasty or vertebroplasty, radiation, or surgical
treatments). A consultation with a treatment specialist may be recommended.
Calcium supplements: Younger than age 50 should
take about 1,000 mg per day; those age 50 and older or
post-menopausal should take 1,200 mg per day.
Do not take calcium supplements if your blood calcium is high or you have decreased
kidney function—discuss with your healthcare provider. Calcium-rich foods include
dairy (i.e., milk, yogurt, and cheese), nondairy (i.e., Chinese cabbage, kale, and broccoli),
and fortified sources (i.e., fruit juices, drinks, tofu, and cereals). Consultation with an
endocrinologist may be recommended.
Vitamin D supplements: Younger than age 50 should
take 400–800 IU per day; those age 50 or older should
take 800–1,000 IU per day
Need for supplement is based on blood levels. Normal levels of vitamin D range from
20–50 ng/ml; discuss with your healthcare provider. Vitamin D is found in animal-based
products such as dairy foods, beef, liver, eggs, fish, and fish oils. Consultation with an
endocrinologist may be recommended.
Self-Care and Health Maintenance
Maintain a balanced diet and hydration (fluid
intake): Try to drink two to three liters (quarts) of fluids
per day
Excess weight can worsen bone pain and muscle fatigue, poor diet intake can worsen
fatigue, and dehydration can worsen fatigue and cause kidney problems. Consultation
with a nutritionist for guidance specific to your dietary needs may be recommended.
Oral hygiene: Practice good oral hygiene and have
dental examinations every six months
Avoid invasive dental work if possible. You may need antibiotics if an invasive
dental procedure is needed. Be sure to inform your dentist if you are taking a bonestrengthening medication.
Exercise and activity: Regular exercise based on
tolerance. No lifting of more than 20 pounds.
Weight-bearing activity promotes bone strength. Consultation with a physical medicine
or spine specialist to determine your activity allowance may be recommended.
Note. This patient education tool may be reproduced for noncommercial use.
Clinical Journal of Oncology Nursing • Supplement to Volume 15, Number 4 • Maintaining Bone Health
19
pain. The pain assessment includes asking a patient about the
following.
• Onset: When did it start? Was trauma involved?
• Location: Where is it located?
• Quality: Dull, sharp, burning, or stabbing?
• Duration: How long have you had this pain?
• Character: Is it present when you sit or move? All the time or
some of the time?
In addition, patients should be asked to rate their pain
according to a pain scale. One of the most common scales
is a 1–10 rating system with 1 as minimal pain and 10 as the
worst pain. Treatment of the pain with analgesics can be
accomplished by using the World Health Organization (2009)
pain ladder. Additional management strategies include the use
of bisphosphonates and systemic antimyeloma therapy that may
have a marked effect on bone pain.
Bone pain from MM can be challenging to control because it
usually occurs when patients change position or walk and is often
called “incident pain.” Three main types of analgesia are used to
treat bone pain and other types of pain related to MM and include
nonopioid analgesics, opioid analgesics, and adjunct medications.
Nonopioid analgesia includes acetaminophen, NSAIDs, and
aspirin. Use of NSAIDs is discouraged because of the risk of
renal injury. Many opioid analgesics exist and also can decrease
pain, but at the expense of sedation and the risk of constipation.
Neuropathic pain often is present after nerve-related injuries such
as in peripheral neuropathy, post-herpetic neuralgia, or spinal
canal compromise and often is described as “burning or shooting”
in character. Medications such as gabapentin or pregabalin, or
tricyclic antidepressants such as amitriptyline, can be helpful in
decreasing this type of pain (Levy, 1996). Systemic antimyeloma
therapy and the use of bisphosphonates will not be effective
in reducing pain in some patients, and this group may require
bracing or surgical intervention.
Effective pain management is imperative because the
psychosocial aspects of pain can lead to depression and anxiety.
In addition, uncontrolled pain will result in immobility and
muscle and bone wasting, in turn leading to increased risks
of atelectasis, pneumonia, and venous thromboembolism.
Healthcare providers must recognize this, diligently monitor
pain scores, and prescribe analgesia to combat these deleterious
side effects (Coleman, 2000).
Patient and Family Education
Nurses play an important role in educating patients as well
as promoting functional independence. Activity can decrease
fatigue as well as improve mood and prevent insomnia.
However, even simple activities can be difficult for patients
with pain. All patients must have effective pain management.
Patients should be educated regarding the use of NSAIDs and
narcotics as educated patients are more likely to adhere to their
therapy. Because bone disease can be debilitating throughout
the continuum of treatment, a dire need exists to instruct
and educate patients and their caregivers regarding the signs
and symptoms of depression and anxiety. Interdisciplinary
collaboration may be required in the education of the patient.
All patients will have varying needs for education regarding
20
their bone health; emphasis on the benefits of treatment will
assist patients in adhering to their therapy.
Educational opportunities include the following.
• Using evidence-based recommendations to promote behaviors
that enhance bone health
• Instructing patients on how to rate pain using a pain scale
• Informing patients about symptoms of hypercalcemia, a
complication of bone disease that includes lethargy, nausea,
confusion, thirst, and constipation
• Enforcing the need for bisphosphonate use; advocating good
oral hygiene while patients are receiving bisphosphonates
• Referring patients to a clinical social worker or psychiatrist
to identify anxiety and depression if necessary
• Counseling to encourage continued adherence to pharmacologic
regimens and exercise programs
Useful resources and tools for patients and caregivers, as well
as nurses and other healthcare providers, can be obtained from
the International Myeloma Foundation at www.myeloma.org.
Conclusion
Recent research in myeloma and the advent of novel agents
has led to increased response rates and improved survival. Bone
disease as a prognostic indicator and therapies directed at bone
disease may alter future treatment regimens and outcomes.
Supportive care and the management of bone disease are of the
utmost importance to alleviate bone-related sequelae, enhance
mobility and disease response, and promote quality of life.
Oncology nurses and other healthcare providers play a crucial
part in assessing and managing myeloma, along with educating
patients, as they live longer and continue to experience both
disease- and treatment-related complications.
The authors gratefully acknowledge Brian G.M. Durie, MD, and
Robert A. Kyle, MD, for critical review of the manuscript; Lynne
Lederman, PhD, medical writer for the International Myeloma
Foundation, for preparation of the manuscript; and Lakshmi
Kamath, PhD, at ScienceFirst, LLC, for assistance in preparation
of the manuscript.
Author Contact: Teresa S. Miceli, RN, BSN, OCN®, can be reached at miceli
[email protected], with copy to editor at [email protected].
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